Ask the Doctors

Dear Doctor: My best friend, who never smoked, died of lung cancer last spring. My father, who has been a smoker since high school, is fine. What puts you at greater risk of getting cancer -- your genes, your habits, the environment, or is it just random chance?

Dear Reader: Your question is familiar ground for anyone whose life has been touched by cancer. It's not so much a wish to assign blame as it is our minds seeking a toehold of logic in the face of catastrophic news. If we know how or why something happened, then life events can be less arbitrary, and thus more manageable.

When it comes to lung cancer, decades of research have substantiated the correlation between the use of tobacco products and lung disease. No, not everyone who smokes goes on to develop lung cancer. But those who smoke, like your father, do increase their risk. However, two recent studies into your question have added some nuance -- and more than a little controversy -- to the discussion.

Please join (and excuse) us as we wonk out a bit.

Last winter, the authors of a paper published in the journal Science returned with a more targeted take. The original paper posed the same questions you're asking. The conclusions led many readers to understand that the authors were saying plain old bad luck is responsible for a majority of cancers. Needless to say, the pushback was fierce.

The newest paper, published by the same authors last March, still comes down on the side of random chance. However, with a larger sample size and expanded explanations and arguments, it also backs many of the ideas behind disease prevention.

The authors wanted an answer to why cancer arises from some tissues in our bodies a million times more frequently than it does in others. They focused on the fact that, in specific tissues that give rise to 31 types of cancer, stem cells divided far more often. Using a mathematical model, they concluded that amid that flurry of DNA replication, errors were occurring.

The new study arrives at the same conclusion: A majority (66 percent) of cancerous mutations result from random chance. However, this time the authors looped in how this relates to environmental factors and genetic predispositions.

Certain behaviors, like smoking, as well as environmental factors and genetics, do cause an increase in mutations. But just where in any individual's DNA these mutations will occur is unpredictable. In your late friend's case, mutations occurred in tissues that gave rise to lung cancer. Your dad's smoking may well have caused mutations as well, but thus far they have not been located in susceptible tissues.

This isn't a blank check to go off the rails. The study concluded that at least three separate gene mutations are needed to move a tissue from health to disease. Maybe one or two mutations will happen due to random chance. Why add to the odds of another mutation by smoking, eating poorly or not getting enough exercise? Bottom line -- when you take part in high-risk behaviors, you're loading the genetic dice.

(Send your questions to askthedoctors@mednet.ucla.edu, or write: Ask the Doctors, c/o Media Relations, UCLA Health, 924 Westwood Blvd., Suite 350, Los Angeles, CA, 90095. Owing to the volume of mail, personal replies cannot be provided.)

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